The purpose of this investigation is to study the in vivo mechanism of tumor regression following immunotherapy using a hapten-modified tumor tissue system. Preliminary work has shown that hapten modification of target tumor by conjugation with L-phenylalanine mustard followed by intravenous administration of antiserum raised against this hapten conjugated with appropriate tumor extract will cause complete regression of both allogeneic and syngeneic rat tumors. In experiments with either allogeneic or syngeneic tumor a single treatment of one of the two bilateral tumors causes complete regression of both. Results indicated that this effect was due to neither PhM alone nor antiserum alone. We consequently found that antiserum against PhM conjugated-carrier protein unrelated to the target tumor was equally effective, thus indicating that both the hapten and antihapten antibody have a role in tumor regression. Histological observation suggested that the reaction may be similar to the Arthus reaction. We will determine the mechanism of tumor regression utilizing syngeneic rat tumor and an active fraction of syngeneic and xenogeneic anti-PhM serum. As a first step, in vitro cytotoxicity of anti-PhM antibody on PhM-treated tumor cells with or without complement will be determined. Similarly the role of polymorphonuclear leukocytes in this regression will be studied. In addition a non-oncolytic hapten (dinitrophenol) will be studied in the same model in order to compare effects.